Human b-cell differentiation. I. Analysis of immunoglobulin heavy chain switching using monoclonal anti-immunoglobulin M, G, and A antibodies and pokeweed mitogen-induced plasma cell differentiation.
Monoclonal antibodies were used to examine the immunoglobulin isotypes expressed by B lymphocyte precursors of IgM, IgG, IgA, and IgA2 plasma cells. Plasma-cell differentiation was induced by the addition of pokeweed mitogen to cultures of blood mononuclear cells. Anti-mu, -gamma, -alpha, and -alpha 1 antibodies were used in some experiments to inhibit differentiation of B lymphocytes bearing these heavy chain isotypes, and for selective removal of B lymphocyte precursors before culture with pokeweed mitogen in other experiments. Three major subpopulations of B lymphocyte precursors were identified: (a) a subpopulation of surface (s) IgM+ precursors of IgM plasma cells that did not express IgG or IgA isotypes, (b) a subpopulation of sIgG+ precursors of IgG plasma cells of which approximately one-half bore some IgM and none had detectable IgA receptors, and (c) a subpopulation of sIgA+ precursors of IgA plasma cells; one half of these precursors could be shown to express functional IgM receptors but none were found to express IgG receptors. The sIgA subpopulation could be further subdivided into sIgA1+ precursors of IgA1 plasma cells and IgA1-negative precursors of IgA2 plasma cells. These results suggest that normal human B cells can switch from mu directly to each of the other heavy chain isotypes, and that these represent the main switch pathways.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000378:metabolism; D007137:Immunoglobulin alpha-Chains / Q000235:genetics / Q000276:immunology; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010950:Plasma Cells / Q000166:cytology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007137:Immunoglobulin alpha-Chains; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; D011043:Pokeweed Mitogens; D011947:Receptors, Antigen, B-Cell